Han Qianqian, Xu Huan, Li Lin, Lei Song, Li Ziyao, Zhao Lijun, Liu Fang
Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
Department of General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2024 Nov 25;15:1474377. doi: 10.3389/fimmu.2024.1474377. eCollection 2024.
More evidence have shown that the combination of immune and inflammatory mechanism was critical in diabetic nephropathy (DN). However, the relationship between CD4+ T cells and the development of DN is still unclear. Therefore, this study will focus on this issue from the perspective of clinicopathology.
From September 2019 to December 2022, a total of 112 adult patients with DN were enrolled in the study. According to the density of CD4+ T cell infiltration based on immunostaining, the patients were divided into high-CD4 group (56 patients) and low-CD4 group (56 patients). Another 25 diabetic patients with minimal change disease (non-diabetic nephropathy, NDN) was reviewed as control group in clinical and molecular analysis. The clinical parameters, morphological features, and molecular characteristics were compared. The predictive value of CD4+ T cells for DN prognosis was also investigated.
DN patients in the high-CD4 group suffered from higher proteinuria and lower estimated glomerular filtration rate (eGFR) level than those in the low-CD4 group and NDN patients. Renal biopsy in the high-CD4 group presented with more severe glomerular lesions, higher density of interstitial inflammation, and more severe tubular atrophy/interstitial fibrosis than in the low-CD4 group. Multivariate logistic analysis indicated that the density of CD4+ T cell infiltration could independently predict the severity of tubular atrophy/interstitial fibrosis. In addition, more severe mitochondrial damage of renal tubular epithelial cells and a more obvious expression of Bcl6, IL-6, STAT3, and TGFβ1 were observed in DN patients of the high-CD4 group, indicating the possible mechanism of CD4+ T cells involving the progression of DN. Multivariate Cox regression analysis revealed that a higher intensity of interstitial CD4+ T cell deposition remained as an independent predictor of the double endpoint with doubling of baseline serum creatinine or end-stage renal disease.
The high density of CD4+ T cell infiltration was associated with renal function decline and severity of renal lesions and predicted poor renal survival for DN patients.
越来越多的证据表明，免疫和炎症机制的结合在糖尿病肾病（DN）中至关重要。然而，CD4+ T细胞与DN发生发展之间的关系仍不清楚。因此，本研究将从临床病理学角度关注这一问题。
2019年9月至2022年12月，共有112例成年DN患者纳入本研究。根据免疫染色显示的CD4+ T细胞浸润密度，将患者分为高CD4组（56例）和低CD4组（56例）。另外25例患有微小病变疾病的糖尿病患者（非糖尿病肾病，NDN）作为临床和分子分析的对照组。比较临床参数、形态学特征和分子特征。还研究了CD4+ T细胞对DN预后的预测价值。
高CD4组的DN患者比低CD4组和NDN患者蛋白尿更高，估计肾小球滤过率（eGFR）水平更低。高CD4组的肾活检显示肾小球病变更严重，间质炎症密度更高，肾小管萎缩/间质纤维化比低CD4组更严重。多因素逻辑分析表明，CD4+ T细胞浸润密度可独立预测肾小管萎缩/间质纤维化的严重程度。此外，在高CD4组的DN患者中观察到肾小管上皮细胞线粒体损伤更严重，Bcl6、IL-6、STAT3和TGFβ1的表达更明显，表明CD4+ T细胞参与DN进展的可能机制。多因素Cox回归分析显示，间质CD4+ T细胞沉积强度较高仍然是基线血清肌酐翻倍或终末期肾病这一双重终点的独立预测因素。
CD4+ T细胞浸润高密度与肾功能下降和肾病变严重程度相关，并预测DN患者肾脏预后不良。
